[Relay toxicity --a new procedure for evaluating toxic effects of additives in animal feed on the animal consumer].
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Biomedical subjects
Publications and source records attributed to R Ferrando.
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DDT induces in young Pigs a rise of hepatic level of cytochrome P 450 and a concomitant decrease of the hepatic "reserve" of retinol. The amplitude of these effects varies according to the hepatic lobe submitted to analysis.
The authors report the underlying principles of the new methodological approach called "relay toxicity" which they proposed eight years ago for the toxicological evaluation of animal feed additives. They stress its value either as a possible criterion of rejection or as a criterion of acceptability. In the latter case, the limiting factor is the difficulty of applying an adequate safety factor when food products destined for human consumption and obtained from animals receiving the additives to be evaluated are administered to laboratory animals. Amongst the examples of the additives which have been subjected to toxicological evaluation using the authors' new method, the following are examined: as growth factor, carbadox, anabolising agents and, in particular, diethylstilboestrol, and steroids used as egglaying potentializers. The results obtained are discussed.
The growth of populations and the spread of urbanization, resulting in new agricultural structures, have entailed a concentration of livestock production and recourse to new techniques. Of some importance among these techniques is the enteric or parenteral administration of substances in very low doses. These substances include anabolic agents, some of which, like many natural feeds, exhibit hormonal activity. They may be divided into two classes: --those of the DES type, synthetic compounds non-existent in the natural state, --natural agents, which are normally distributed throughout the animal and human organism, and hence in food of animal origin---milk, meat, eggs. The compounds belonging to the second class may also be synthesized and the main toxicological consideration is that they then have to meet clear-cut standards of identity and purity. A compound belonging to the first class, diethylstilbestrol (DES), administered to rats in doses as small as 60 mug/kg of feed or even smaller, causes in general lower growth rates as well as alterations in the genital system and reproductive functions. In long-term experiments (12 months) using rats and mice and applying so-called toxicity "de relais" tests, developed and described by the authors, it also appeared that meat from calves in which DES pellets were implanted under normal rearing conditions, inhibits growth and reproduction in mice and rats fed a diet containing 20% of this meat. Studies in which the livers from treated calves constituted 6% of the diet of these two rodent species also led to the conclusion that fertility was impaired in the second reproduction test. The authors also recall cases of vaginal cancer observed in young girls whose mothers had been treated with DES during pregnancy. Compounds belonging to the second class (estradiol-progesterone and estradiol-testosterone) gave no evidence of harmful effects upon rats when mixed with their rations during short and medium-term trials. Similar results were obtained from studies with rats and mice fed a diet containing 20% veal or 6% liver of calves in which pellets of these natural hormones had been implanted. In these studies, which lasted 23--24 months with rats and 347 days with mice, the toxicity "de relais" test was applied under similar conditions to those undertaken using meat and livers of implanted calves. The report also refers to trenbolone and to "zéralénone" but no toxicity "de relais" tests were carried out with the meat and livers of animals treated with these substances. The authors reached the following conclusions: DES should not be used as an anabolic agent in livestock production. Natural hormones prepared through synthesis or otherwise could be used as anabolic agents in livestock production since no risk to the consumer has been witnessed when they were administered at doses similar to those used in the author's experiments. However, it is recommended that they should be applied under veterinary supervision...
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Vitamin A, a good adjuvant to immunologic reactions, has in this aspect an interesting therapeutic effect, especially in immunotherapy. On the other hand, in diseases caused by circulating immunocomplexes or in auto-immune diseases, vitamin A can prolong the pathologic immunologic process. This experimental study shows that vitamin A in high doses has an adjuvant effect, that is aggravating considerably the immunologic arthritis induced in the Wistar rat.
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Chemical substances added for various purposes to the feeds of farm-reared animals may enter the body of these animals. This may lead to the persistence, in food offered for human consumption, of residues which may be potentially toxic under conditions of repeated absorption over the greater part of the life span. The evaluation of the safety of these residues for man poses complex problems. Their ideal solution demands very often a number of careful experiments. The methodology called "toxicity by relay" consists essentially of the submission of the animal feed itself, which is likely to contain a mosaic of residues, to long-term testing in laboratory animals. Provided a satisfactory safety factor can be applied, this methodology can contribute information permittinga conclusion regarding the acceptablity, even provisionally, of the feed additive for the use which is envisaged. In addition this methodology enables the provision of results constituting a criterion for the rejection of the additive under test. For these reasons it appears to us an appropriate procedure, taking its place among the tests to be undertaken for the toxicological evaluation of additves to the feeds of farm-reared animals.
A toxicity by relay. II. A method for the assessment of safety to human consumers of carbadox, a growth-promoting additive to the feed of slaughter pigs. A new methodology called "toxicity by relay" has been used to assess the potential hazard to humans of incorporating an additive into animal feeds. This methodology considers a farm-reared animal as a "relay" between the food additive and the human consumer, and employs laboratory animals as "pseudo-consumers". These laboratory animals are fed throughout their entire lives with the meat or organs of the "relay" animals which have been reared on feeds supplemented with various levels of the additive. In the present study, the toxicity of carbadox was assessed in this way. In pigs, where it is used as a growth promoter, carbadox is metabolised into serveal different products, and so an assessment of its safety using traditional methods of studying the toxicity of a substance and tis known metabolites, would perhaps be subject to error. A safety factor for man, in relation to the safety factors for rats and dogs, was calculated using (a) the comparative consumption of the laboratory animals and man; (b) an assessment of the highest dosage likely to be consumed in normal circumstances compared to the laboratory dosage, and (c) the consideration that in the laboratory there is no period of withdrawal from feeding before sacrifice as is the case with animals for slaughter. Pigs were used as "relays" in the present study by supplementing their feed with carbadox. The meat and/or livers of these animals were then fed daily to (a) rats for a period of 3 generations; (b) rats for 24-25 months, and (c) dogs for 60 months. No abnormalities were observed at the termination of the experiments. We may therefore conclude that there is no hazard for the human consumer from the use of carbadox as a pig-feed additive.
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Duckling are feeding peanut and meal detoxified or not by ammonia at the level of 25 p. 100. Control group are eating soybean meal at the same level. The raw protein content of diet is the same in each group. Experiment is carried out during four weeks, then duckling are killed. There is no significative difference between peanut meal detoxified and soybean meal relating to growth and food efficiency. Thus body weight is 775 and 764 g on duckling eating soybean meal; 764 and 827 g on duckling with peanut meal detoxified but only 472 and 452 g on birds with diet containing peanut meal not detoxified by NH3. Liver's weight is increased on these subjects. The ratio of liver weight to body weight X 100 is 5,49-4,79 and, respectively, 2,70-3,60 and 3,86-3,56 on duckling with detoxified peanut meal or controls eating soybean meal. Characteristic lesions of aflatoxicosis are developed on duckling consuming peanut meal not detoxified dosing about 285 mug/kg of Aflatoxin B1. Lesions are very slight, but present, on liver and kidney in detoxified peanut meal fed duckling. For kidney's lesions there are no differences between detoxified or not group, duckling eating detoxified peanut meal have absorbed 0,4 mug of Aflatoxin B1 during the eight first days of experiment and 8 to 10 mug during four weeks. These considerations explain light lesions observed and underlines duckling's sensitivity regarding aflatoxicosis.
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